Angiotensin metabolite profile after subarachnoid hemorrhage

Subarachnoidal bleedings are most often caused by the rupture of a morbidly enlarged brain artery. A frequent complication within the first week after the bleeding is the development of a cramp of the brain blood vessels that may reduce perfusion of the brain so dramatically that a stroke followed by lasting disability or even death may occur. The renin-angiotensin system (RAS) plays a role in the regulation of blood pressure and the body fluid household, and is involved in many cardiovascular and pulmonary diseases. It is a network of enzymes that cut proteins the angiotensins into smaller pieces that have their own biological functions. Renin cuts angiotensinogen to angiotensin I (Ang I). Subsequently, Ang I is cut by angiotensin converting enzyme (ACE) producing Ang II that may be further split into smaller angiotensins by ACE2 and other enzymes. Shortly after a subarachnoidal bleeding there is a strong activation of the RAS with increased concentrations of renin and Ang II in the blood. Ang II is a potent constrictor of blood vessels, but if it plays a role for development of the cramp of the brain vessels after a subarachnoidal bleeding has not yet been investigated. Up to two thirds of patients with this type of bleeding need mechanical ventilation for some time, which may also activate the RAS. A high blood pressure is an important risk factor for subarachnoidal bleedings and the ensuing brain vessel cramp, and about half of the affected patients have a history of high blood pressure. Furthermore, high blood pressure is a medical problem at the time of weaning from sleeping medication and mechanical ventilation, but if the known antihypertensive drugs that act on the RAS display the expected effects also in these patients is not clear. As the activity of the RAS may already be changed, the effects of these drugs could be altered in these patients. This study will investigate the main actors of the RAS after subarachnoidal bleedings, which are the angiotensins and the enzymes ACE and ACE2 in the blood and ACE and ACE2 in the cerebrospinal fluid. The investigation of the cerebrospinal fluid is possible, because often drainage of this fluid is necessary to avoid its accumulation after the bleeding. These investigations will be done weekly during the stay in the intensive care unit for up to three weeks. Another blood sample will be taken as soon as an antihypertensive drug that acts on the RAS has been started in the intensive care unit to have a look which effects on the RAS may be achieved by this therapy. The results of this study will show, if patients with a cramp of the brain vessels, ventilated patients or patients with more severe bleedings show a different regulation of the RAS, and if the use of antihypertensive drugs that act on the RAS is helpful in patients with this disease.